We are investigating the pathophysiology of acute pulmonary edema with special reference to plasma colloid osmotic pressure. Pulmonary edema is usually caused by alteration of either colloid-hydrostatic driving pressure or capillary membrane permeability. The extent to which reduction in plasma colloid osmotic pressure potentiates the development of pulmonary edema by critical alteration of the plasma colloid osmotic pressure-pulmonary micro-vascular hydrostatic pressure gradient is studied. Parallel investigations are conducted in the experimental laboratory and in our clinical Shock Research Unit. The relationsiip of plasma colloid osmotic pressure, pulmonary microvascular hydrostatic pressure, and intravascular volume is studied in an animal model of the nephrotic syndrome. The therapeutic implication of volume loading with crystalloid versus colloid fluids is subsequently studied in this nephrotic animal model. Observations concerning the development of pulmonary edema during crystalloid and colloid volume loading in hypotensive patients with the nephrotic or cirrhotic syndromes are then made in our clinical Shock Research Unit. In the experimental laboratory, extravascular lung water is measured by the double indicator-dilution technique and lung wet/dry ratio corrected for residual blood volume. Pulmonary edema is evaluated in the clinical setting by chest roentgenography and double indicator-dilution measurement of extravascular lung water. The development of pulmonary edema is serially studied coincident with the determination of plasma colloid osmotic pressure-pulmonary microvascular hydrostatic pressure gradient. Measurement of tracheal fluid protein content identifies coincident changes in pulmonary vascular membrane permeability, so that such patients may be separately classified.